How SPILLO-PBSS helps improving rational design of animal testing
The knowledge of the SPILLO-PBSS identified potential target proteins of a xenobiotic, along with the structural details concerning the protein binding sites provided by the software, allow to carry out cross-species transferability analyses between humans and other organisms (e.g., from Homo sapiens to Rattus norvegicus), and vice versa. This can help to assess the reliability of an animal model in advance, for an improved rational design of animal testing and a better interpretation of the results.
|Possible checks and evaluations to help assess the reliability of an animal model|
|1||→ Check whether the SPILLO-PBSS identified (e.g., in Homo sapiens) potential target proteins of the xenobiotics are present in the model organism (e.g., Rattus norvegicus)|
|2||→ Calculate the overall sequence identity between the human target protein and the same protein in the model organism|
|3||→ Verify the local similarity between the xenobiotic binding site within the human target protein and the corresponding binding site within the protein of the model organism (by applying SPILLO-PBSS to a 3D homology model of the model organism protein)|
These checks, if carried out in advance, can make it possible to avoid unnecessary experiments and to design animal testing in a more targeted manner, according to the 3Rs principle.
Then, for a better interpretations of the results, the same kind of analysis can also be carried out starting from the target proteins (of a xenobiotic) of the model organism (e.g., Rattus norvegicus), to assess the transferability of the results to Homo sapiens.
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Comparison with traditional structure-based approaches
Identifying target proteins responsible for toxic effects of xenobiotics
Rational polypharmacology drug design AND Optimization of drug safety profile
Main applications of SPILLO-PBSS to the drug R&D process
A short description of SPILLO-PBSS
Experimental validation published in peer-reviewed scientific journal